Endocrine hypertension, phaeochromocytoma and congenital adrenal hyperplasia
Which hypertensive patients need a hormone work-up, how to diagnose and treat primary hyperaldosteronism and phaeochromocytoma, and the forms of congenital adrenal hyperplasia.
UHS PGET syllabus: Endocrinology (10 MCQs), Investigate suspected endocrine hypertension (phaeochromocytoma); congenital adrenal hyperplasiaUpdated October 2026Share on WhatsApp
In 30 seconds
Look for an endocrine cause of high blood pressure in the young, the resistant, those with hypokalaemia and those with attacks of headache, sweating and palpitations.
Conn's syndrome: high aldosterone, low renin, hypokalaemic alkalosis; screen with the aldosterone : renin ratio. Phaeochromocytoma: screen with plasma or urinary metanephrines; give an alpha-blocker before a beta-blocker, then operate.
CAH is autosomal recessive; 21-hydroxylase deficiency causes raised 17-OHP, virilised girls and salt-losing crises in newborn boys.
On this page
Overview
Most high blood pressure is essential, but a small group has a hormonal cause that can often be cured. The main endocrine causes are primary hyperaldosteronism, phaeochromocytoma, Cushing syndrome, acromegaly and, rarely, some forms of congenital adrenal hyperplasia (CAH).
CAH is a group of inherited defects in cortisol synthesis. It is the commonest cause of ambiguous genitalia in girls and of adrenal failure in childhood.
Renal artery stenosis, other renal disease, renin-secreting tumour
Too much catecholamine
Phaeochromocytoma, paraganglioma
Too much cortisol (weak mineralocorticoid action)
Cushing syndrome
Too much growth hormone
Acromegaly
Other mineralocorticoids
CAH (11β- and 17α-hydroxylase types), liquorice, mineralocorticoid misuse
Whom to screen
It is not practical to test every hypertensive patient. Look for a secondary cause when the patient:
is young (under about 35), especially without a family history;
has accelerated (malignant) hypertension;
has hypokalaemia (unprovoked, or marked on a low diuretic dose);
has resistant hypertension (not controlled on three or more drugs);
has unusual symptoms: sweating attacks, palpitations, headaches, muscle weakness;
has an adrenal mass found by chance.
Primary hyperaldosteronism
Pathophysiology
Autonomous aldosterone from the zona glomerulosa causes sodium retention, potassium loss and hydrogen ion loss. Renin is suppressed. Sodium stays high-normal and oedema is unusual because the kidney "escapes" after a few days of sodium retention.
It accounts for roughly 5–10% of hypertension, making it the commonest endocrine cause.
Type
Notes
Bilateral adrenal hyperplasia (idiopathic)
Now known to be the commonest form; older patients, more often men
Rare; chimeric gene puts aldosterone synthesis under ACTH control; treated with a glucocorticoid
Clinical features
Usually just hypertension, which may be severe with target-organ damage.
Hypokalaemia is often absent, so a potassium in the normal range should not reassure you.
When potassium is low: muscle weakness, polyuria and nocturia (kidney cannot concentrate urine), rarely tetany (alkalosis).
Investigations
Aldosterone : renin ratio (ARR) is the screening test. Stop or adjust interfering drugs first where safe: spironolactone, ACE inhibitors, angiotensin receptor blockers, diuretics and beta-blockers all change renin. Correct hypokalaemia.
Confirm that aldosterone fails to suppress: saline infusion test (2 L of 0.9% saline over 4 hours) or fludrocortisone test. Many people with a raised ARR suppress normally and do not have the disease.
Other clues: low renin, hypokalaemia with inappropriate urinary potassium loss (above 30 mmol a day despite low serum K), metabolic alkalosis.
Find the subtype: adrenal CT or MRI, then adrenal vein sampling to show whether one or both glands are overactive (small adenomas and non-functioning incidentalomas cause confusion on imaging).
Management
Adenoma:laparoscopic adrenalectomy; blood pressure improves in most.
Bilateral hyperplasia:spironolactone (side effects: gynaecomastia, nausea, rash) or eplerenone if not tolerated. Amiloride is an alternative.
High-yield
In a hypertensive patient, hypokalaemia with metabolic alkalosis and a suppressed renin is primary hyperaldosteronism until shown otherwise.
Exam trap
Primary hyperaldosteronism has low renin. Secondary hyperaldosteronism (renal artery stenosis, diuretics, heart failure, cirrhosis) has high renin. Both can show high aldosterone and hypokalaemia.
Look-alikes with low renin and low aldosterone
Condition
Mechanism
Clue
Liquorice excess
Inhibits 11β-HSD2 in the kidney, so cortisol is not inactivated to cortisone and acts on the mineralocorticoid receptor
History of liquorice sweets or herbal remedies
Apparent mineralocorticoid excess (inherited)
Same enzyme defect
Child with severe hypertension
Liddle syndrome
Overactive epithelial sodium channel (ENaC) in the collecting duct; autosomal dominant
Young, family history; responds to amiloride, not spironolactone
Phaeochromocytoma and paraganglioma
What it is
A rare catecholamine-secreting tumour of chromaffin cells (fewer than 1 in 1000 hypertensive patients).
About 90% arise in the adrenal medulla (phaeochromocytoma); about 10% are extra-adrenal in the sympathetic chain, head and neck, chest, pelvis or bladder (paraganglioma).
Kumar notes about a quarter are multiple and about 10% malignant; malignancy is more common in extra-adrenal tumours and cannot be judged from histology alone.
Most secrete both noradrenaline and adrenaline; large and extra-adrenal tumours make mainly noradrenaline.
Tumour cells stain for chromogranin A.
Inherited associations (suspect in young, bilateral, extra-adrenal or familial cases): MEN 2A and 2B, von Hippel–Lindau syndrome, neurofibromatosis type 1, and succinate dehydrogenase (SDHB, SDHD) mutations (paragangliomas). Genetic testing is advised for every confirmed case.
Hypertension, sustained or paroxysmal; tachycardia or arrhythmias.
Postural hypotension (volume is contracted by chronic vasoconstriction).
Hyperglycaemia or glycosuria.
Attacks can be triggered by exertion, anaesthesia, surgery, labour or certain drugs. An undiagnosed tumour can cause sudden death during a routine procedure.
Plasma metanephrines or 24-hour urinary metanephrines
Most sensitive and specific; normal results virtually exclude the diagnosis. Tricyclics, some other drugs and stress can cause false positives
Plasma chromogranin A
Raised
Clonidine suppression test
Specialist centres, for borderline results
2. Localisation
CT or MRI of the abdomen
Tumours are usually large
MIBG scan (meta-iodobenzylguanidine)
Picks up sympathetic tissue; useful for extra-adrenal and metastatic disease
PET (FDG or newer tracers)
Used in some centres
3. Genetics
MEN 2 (RET), VHL, SDH genes
All confirmed cases
High-yield
Biochemical proof comes before imaging. Image only after metanephrines are raised; otherwise an incidental adrenal lump will mislead.
Management
Alpha-blockade first:phenoxybenzamine (non-selective, irreversible alpha-blocker), started well before surgery.
Liberal fluids and salt (or IV fluids) to re-expand the contracted plasma volume.
Then add a beta-blocker (e.g. propranolol) for tachycardia, only after alpha-blockade is established.
Surgical removal (usually laparoscopic) by an experienced team. During surgery, phentolamine (short-acting alpha-blocker), sodium nitroprusside and magnesium are kept ready for hypertensive surges; hypotension is common once the tumour is out.
If surgery is impossible, long-term combined alpha- and beta-blockade; MIBG therapy has a limited role in malignant disease.
Exam trap
Giving a beta-blocker first leaves alpha receptors unopposed: vasoconstriction worsens and a hypertensive crisis can follow. Labetalol is not recommended as the main agent.
Prognosis is good for benign tumours (5-year survival about 95%), but lifelong follow-up with metanephrines is needed because tumours can recur.
Adrenal incidentaloma
An adrenal mass found by chance on scanning (in a few per cent of abdominal scans, more with age). Ask two questions:
Is it functioning? Test for cortisol excess (overnight dexamethasone), phaeochromocytoma (metanephrines) and, if hypertensive or hypokalaemic, aldosterone (ARR).
Is it malignant? Large size (above about 4–5 cm) and irregular appearance raise concern; these are usually removed.
Exam trap
Exclude phaeochromocytoma before any adrenal biopsy or surgery, as handling the tumour can cause a fatal crisis.
Congenital adrenal hyperplasia (CAH)
Pathophysiology
Autosomal recessive defects in enzymes of cortisol synthesis.
Low cortisol → no feedback → high ACTH → adrenal hyperplasia.
Precursors before the block pile up and are diverted to whatever pathway is still open, usually androgens.
Recurrence risk for parents who already have an affected child: 1 in 4.
Hypertension, hypokalaemia; under-virilised boys, absent puberty in girls
3β-hydroxysteroid dehydrogenase
Low
Low
Weak androgens
Low
Salt loss; ambiguous genitalia in both sexes
Lipoid CAH (StAR or side-chain cleavage)
Low
Low
Low
Low
Severe salt loss; all appear female
High-yield
21-hydroxylase deficiency is by far the commonest form; the screening and diagnostic marker is a raised 17-hydroxyprogesterone.
Memory hook
Enzymes with a 1 in the name (11β, 17α) raise blood pressure; 21 loses salt.
21-hydroxylase deficiency
Genetics: CYP21A2 gene on chromosome 6, close to the HLA region; about 1 in 15,000 births.
Classical (salt-wasting and simple virilising) forms:
Girls:ambiguous genitalia at birth (clitoral enlargement, labial fusion); internal organs (uterus, ovaries) are normal.
Boys: genitals look normal, so they present with a salt-losing adrenal crisis in the first one to two weeks: vomiting, dehydration, weight loss, hyponatraemia, hyperkalaemia, hypoglycaemia, shock. Increased pigmentation of the scrotum and nipples may be seen.
Untreated simple virilisers: early pubic hair, rapid growth, advanced bone age and short final height (early epiphyseal fusion).
Non-classical (late-onset) form: presents in childhood or adult life with precocious puberty, hirsutism, acne, oligomenorrhoea or infertility in women; can mimic polycystic ovary syndrome. Hirsutism starting before puberty suggests CAH.
Investigations
Serum 17-hydroxyprogesterone (17-OHP): markedly raised. Neonatal screening on dried blood spots is used in many countries.
If not clearly raised, a Synacthen test with 17-OHP measured at 0 and 60 minutes; Kumar takes a level above 30 nmol/L at baseline or after stimulation as confirming 21-hydroxylase deficiency.
Urea and electrolytes, glucose, plasma renin (high in salt loss).
Karyotype and pelvic ultrasound in any baby with ambiguous genitalia; expert team review before gender is assigned.
Management
Salt-losing crisis: IV 0.9% saline, glucose, IV hydrocortisone (as for adrenal crisis).
Long-term:glucocorticoid replacement (hydrocortisone in children) to replace cortisol and suppress ACTH-driven androgens; fludrocortisone and salt supplements in salt losers.
Monitor growth velocity, bone age, 17-OHP, androstenedione and renin. Too much steroid stunts growth; too little allows virilisation and early fusion.
Sick day rules and an emergency hydrocortisone kit, as in Addison disease.
Genital surgery in selected girls; psychological support; genetic counselling. Antenatal dexamethasone to reduce virilisation of an affected girl is controversial.
Exam trap
In a newborn with vomiting and dehydration, pyloric stenosis causes hypokalaemic alkalosis, whereas salt-losing CAH causes hyperkalaemia with low sodium. Potassium tells them apart.
Exam focus
Expect: which hypertensive patients to screen; Conn's syndrome with hypertension, hypokalaemia, alkalosis and low renin; aldosterone : renin ratio as the screen and the effect of drugs on it; adenoma versus bilateral hyperplasia and spironolactone; liquorice and Liddle syndrome (low renin, low aldosterone); phaeochromocytoma triad, metanephrines, MIBG for extra-adrenal tumours, alpha-blocker before beta-blocker, MEN 2 and VHL links; exclude phaeochromocytoma before touching an adrenal mass; 21-hydroxylase deficiency with raised 17-OHP, ambiguous genitalia in girls and salt-losing crisis in boys; hypertensive CAH forms (11β and 17α).
Conn's: aldosterone up, renin down, K down, alkalosis, no oedema; ARR then saline suppression; CT and adrenal vein sampling.
Adenoma → adrenalectomy; bilateral hyperplasia → spironolactone or eplerenone.
Liquorice, apparent mineralocorticoid excess and Liddle: low renin and low aldosterone; Liddle responds to amiloride.
Phaeochromocytoma: headache, sweating, palpitations; metanephrines; CT/MRI then MIBG; phenoxybenzamine, fluids, then beta-blocker, then surgery.
Phaeochromocytoma links: MEN 2, VHL, NF1, SDH; genetic testing for all.
CAH: autosomal recessive; 21-hydroxylase commonest; 17-OHP raised; girls virilised, boys salt-lose at 1–2 weeks.
11β- and 17α-hydroxylase deficiency: hypertension with hypokalaemia.
Written by The House Job from standard references (Kumar and Clark's Clinical Medicine; Basis of Paediatrics).
FAQ
Why is oedema uncommon in primary hyperaldosteronism?
After an initial gain of sodium and water the kidney increases sodium excretion again (aldosterone escape), so body sodium stops rising and oedema does not develop.
Why must a beta-blocker never be started first in phaeochromocytoma?
Blocking beta receptors removes beta-2 vasodilation and leaves catecholamines acting only on alpha receptors, so blood pressure can rise sharply.
What is the best first test for suspected phaeochromocytoma?
Measurement of metanephrines in plasma or in a 24-hour urine collection, because these metabolites are produced continuously by the tumour.
Why do baby boys with CAH present later than baby girls?
Girls are noticed at birth because of virilised genitals, whereas boys look normal and are only recognised when a salt-losing crisis develops in the first weeks.
How can CAH cause high blood pressure?
In 11β- and 17α-hydroxylase deficiency the precursor 11-deoxycorticosterone builds up; it acts as a mineralocorticoid, retaining salt and losing potassium.
